Related Experiment Video

Updated: Oct 9, 2025

Bio-layer Interferometry for Measuring Kinetics of Protein-protein Interactions and Allosteric Ligand Effects
13:57

Bio-layer Interferometry for Measuring Kinetics of Protein-protein Interactions and Allosteric Ligand Effects

Published on: February 18, 2014

29.7K

Allosteric Inhibition of Acinetobacter baumannii ATP Phosphoribosyltransferase by Protein:Dipeptide and

Benjamin J Read1, Gemma Fisher1, Oliver L R Wissett1

  • 1School of Biology, Biomedical Sciences Research Complex, University of St Andrews, St Andrews, Fife KY16 9ST, United Kingdom.

ACS Infectious Diseases
|December 20, 2021
PubMed

Insights

Acinetobacter baumannii ATP phosphoribosyltransferase (ATPPRT) has a unique rapid equilibrium random kinetic mechanism. Understanding its inhibition by histidine and histidine-proline is key for developing new antibiotics against pneumonia.

Area of Science:

  • Biochemistry
  • Microbiology
  • Drug Discovery

Background:

  • ATP phosphoribosyltransferase (ATPPRT) is crucial for histidine biosynthesis in bacteria.
  • In Acinetobacter baumannii, ATPPRT is essential for lung persistence during pneumonia.
  • Targeting ATPPRT presents a promising strategy for novel antibiotic development.

Purpose of the Study:

  • To elucidate the kinetic mechanism of Acinetobacter baumannii ATPPRT.
  • To characterize the inhibition kinetics of histidine and histidine-proline on A. baumannii ATPPRT.
  • To explore the inhibitory potential of related HisZ proteins.

Main Methods:

  • Enzyme kinetics assays were employed to determine the reaction mechanism.
  • Binding kinetics and rapid kinetics analyses were performed to study inhibitor interactions.
  • Sequence identity comparison was used for related HisZ proteins.

Main Results:

  • A. baumannii ATPPRT exhibits a unique rapid equilibrium random kinetic mechanism.
  • Histidine noncompetitively inhibits ATPPRT, binding with similar affinity to various enzyme complexes.
  • Histidine-proline inhibits ATPPRT competitively against PRPP and uncompetitively against ATP, binding via a two-step mechanism.

Conclusions:

  • The unique kinetic properties of A. baumannii ATPPRT offer specific inhibition opportunities.
  • Understanding the binding of histidine and histidine-proline provides a basis for rational inhibitor design.
  • A related HisZ protein acts as a potent allosteric inhibitor, further supporting therapeutic targeting.

Keywords:
ATP phosphoribosyltransferaseAcinetobacter baumannii, kinetic mechanismenzyme inhibitionprotein:protein interaction

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